The objectives of this investigation are (1) to isolate and characterize the factor(s) in polymorphonuclear leukocytes responsible for producing the pulmonary destruction characteristic of experimental emphysema in the dog and human and (2) to determine the lung macromolecule degraded or altered during emphysema development. Leukocyte acetone powder extracts, previously shown to preduce experimental emphysema in dogs, will be fractionated using standard biochemical procedures in order to purify the factor(s) inducing pulmonary emphysema. Both in vivo and in vitro procedures will be quantitated and utilized to serve as assay systems to monitor the purification methods. The intact animal (in vivo model) and two types of in vitro assay are presently being employed, i.e. lesion induction in isolated lobes of dog lungs and hydrolysis of various connective tissue fractions isolated from dog lungs. Purification of the active factor will be paralleled by the continuing biochemical definition of the specific lung component altered during experimental emphysema formation.